Although the interpretation of the markers requires a critical appraisal of the staining outcome in relation to the clinical history and the overall morphology, there are still a few cornerstones in diagnostic pathology that we believe are of direct value when interpreting NEN-Ups: (1) identify an epithelial origin to exclude pheochromocytoma/paraganglioma; (2) screen widely with TTF1, PDX1 and CDX2; and (3) verify with site-specific stainings (Figure 8). This evidence concerns the gene PDX1 and hereditary pheochromocytoma-paraganglioma.